Intradermal versus Intramuscular Administration of Influenza Vaccination: Rapid Review and Meta-analysis

Background Vaccinations are essential for prevention of influenza. We synthesized the published literature on the immunogenicity and safety of the influenza vaccine at reduced or full intradermal doses compared with full intramuscular doses. Methods A rapid review of the literature was completed. MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched for studies published from 2010 until June 5 th , 2020. All studies comparing intradermal and intramuscular influenza vaccinations were included. Random-effects meta-analyses of immunogenicity and safety outcomes were conducted. Results A total of 30 relevant studies were included. Seroconversion rates were equivalent between the 3 mcg, 6 mcg, 7.5 mcg, and 9 mcg intradermal vaccine doses and the 15 mcg intramuscular vaccine dose for each of the H1N1, H3N2, and B strains, but significantly higher with the 15 mcg intradermal compared with the 15 mcg intramuscular dose, for the H1N1 (RR 1.10, 95% CI: 1.01-1.20) and B strains (RR 1.40, 95% CI: 1.13-1.73). Seroprotection rates for the 9 mcg and 15 mcg intradermal doses were equivalent with the 15 mcg intramuscular dose for all the three strains, except for the 15 mcg intradermal dose for the H1N1 strain which was significantly higher (RR 1.05, 95% CI: 1.01-1.09). Local adverse events were significantly higher with intradermal doses. Fever and chills were significantly higher with the 9 mcg intradermal dose, while all other systemic adverse events were equivalent for all doses. Conclusion Reduced dose intradermal influenza vaccination appears to be a reasonable alternative to standard dose intramuscular vaccination because of the similarity in immunogenicity.